Menopause and the Microbiome

Menopause is a crucial part of every woman’s life course, marking the transition from active reproductive function to declining sex hormone production.

Along with menopause and age, women’s health undergoes major changes, including the risk of cardiovascular disease and diabetes. Many factors contribute to menopausal well-being, including the microbiome.

The gut microbiome in women’s health

Sexual dimorphism is a characteristic of the gut microbiome, occurring first towards puberty and in adolescence as the microbiome shifts towards adulthood. This implicates the role of sex hormones in shaping the gut microbiome.

Age-related shifts in the gut microbiome have also been reported.

The gut microbiome contributes to the metabolism of dietary fiber, amino acids, bile acids, hormones including estrogens (female sex hormones), and also synthesizes lipopolysaccharides, which form part of the cell wall of gram-negative bacteria and are extremely toxic to the host.

The gut microbiome is also part of a broader network, forming a key component of the gut microbiota-brain axis whereby the brain and the gut interact with each other through metabolites, neuroendocrine, and immune pathways.

With continued growth and development, the individual’s immunity, diet and other lifestyle factors, metabolic direction, medical condition, and mucosal integrity, may continue to show increasing shifts, causing greater microbiome diversity between adults.

Diversity in this area reaches a stable peak at about 40 years. Each person eventually develops a unique microbiota with age.

While women have a richer gut microbiome composition than men, with a lower abundance of Prevotella, this diversity fades with age. This indicates that men and women age differently with respect to the microbiome, probably due to the effects of menopause.

Menopause and the gut microbiome

It is known that the gut microbiome in postmenopausal women resembles that of men more than premenopausal women. It also shows lower microbial diversity. Some consistent trends have been observed, such as a lower abundance of Firmicutes/Ruminococcus, and increases in Prevotella, Sutterella, Dorea, and Butyricimonas.

Ruminococci are known to ferment fiber and to produce short-chain fatty acids (SCFAs) that are beneficial to health. Conversely, the latter genera are linked to obesity.

In menopausal women, the concentrations of Odoribacter are raised, leading to increased levels of SCFAs as well as hydrogen sulfide. High levels of SCFAs could result in a rise in fatty acid breakdown and higher energy substrate use. This is associated with higher serotonin synthesis, greater neuronal stability, and better osteogenesis. 

Biophila species increase in abundance following menopause, causing hydrogen sulfide (H2S) production. H2S leads to the relaxation of the ileal smooth muscle, improving the blood supply of the gut mucosa.

At excessive levels of H2S, as occurs after menopause, local inflammation sets in within many tissues, damaging the mucosa, and causing increased serum endotoxin levels.

Inflammation leads to insulin resistance via impaired insulin activity on target cells. In the central nervous system, inflammatory factors cross the blood-brain barrier to induce microglial activation. The resulting neuronal inflammation could lead to tau tangles and beta-amyloid protein, promoting the onset of Alzheimer’s disease.

Within the bone, inflammation causes increased osteoclast function, wearing down the bone tissue and leading to osteopenia. However, these changes are related more strongly to gut microbiota changes than to vaginal microbiome shifts.

Thus, a rise in Odoribacter is linked to both beneficial and adverse effects in menopausal women.

Maintaining sex hormone levels in menopause

The gut microbiome is known to break down sex hormones among other chemicals. In postmenopausal women, about 50% of estrogens in circulation are excreted in the bile, but only about 10-15% are excreted in the feces in conjugated or inactive form.

In other words, some gut microbes can deconjugate estrogens, thus allowing them to be reactivated after being reabsorbed into the enterohepatic circulation.

The sum of the bacterial genes involved in this process is termed the estrobolome. The major bacterial species acting to deconjugate estrogens are from Firmicutes and Bacteroidetes.

This may be true of progesterone as well. Thus, while the sex hormones feed or regulate microbial metabolic pathways, their levels are restored in part by the microbiota. This could be of importance in determining the serum sex hormone levels in postmenopausal women, where the ovarian synthesis of estrogens and progesterone is extremely low.

“The impact of estrobolome activity on hyperestrogenic conditions such as estrogen-mediated malignancies (for example, breast, ovarian and endometrial cancers) is another controversial topic that might be elucidated in future studies.”

Osteoporosis is another potential consequence of menopause-associated changes in the gut microbiome. In a recent study, osteopenic, post-menopausal patients showed higher abundances of species like Fusicatenibacter, Lachnoclostridium, and Megamonas.

Genitourinary microbiome and menopause

Following menopause, the vaginal microbiota is characterized by reduced Lactobacillus species, while anaerobic species such as Gardnerella, Prevotella, Anaerococcus, Peptoniphilus and Peptostreptococcus are consistently found to be present.

Though these are typical of bacterial vaginosis (BV) in the premenopausal woman, in older women the levels of these microbes are low, thus ensuring a reduced prevalence of BV in these women.

Skin and gut microbes like Escherichia, Enterococcus, Streptococcus, Staphylococcus, and Corynebacterium are also often present in the vagina following menopause.

The vaginal dysbiosis, of which the hallmark is a shift in Lactobacillus profiles, is linked to urinary urgency as well as incontinence, interstitial cystitis with bladder pain syndrome, and neuropathic bladder – the genitourinary syndrome of menopause (GSM).

Also, some shifts in the uterine microbiome, such as the detection of Porphyromas somerae, may act as markers for endometrial cancer risk in certain groups of women.

Is hormone replacement therapy helpful in attenuating these changes in the menopausal gut? More research is needed to answer this question, because of diverse lifestyles, dietary patterns, and medical conditions, as well as a lack of studies in humans in this field.

Hormone replacement therapy is known to restore the health of the genitourinary microbiome in part. Women with GSM could be potentially treated by supplementation with estrogen or Lactobacillus, or probably a combination of both.

Changes to the vaginal microbiome could have an important impact on the arising of lower urinary tract diseases. This warrants more research on the effects of menopause-associated alterations in the urinary microbiome on urinary tract disease.

Menopause and microbial translocation

Microbial translocation is the phenomenon whereby gut microbiota enters the systemic circulation via the intestinal wall. This involves their overcoming the mucus and epithelial barriers and evading resident macrophages.

The result of this translocation is systemic inflammation, as seen in inflammatory bowel disease (IBD).

Estrogen and progesterone are closely linked to intestinal epithelial barrier integrity. Estrogen protects mucus cells from oxidative injury, maintains an impermeable epithelial barrier, and improves barrier function, while progesterone levels are inversely associated with lipopolysaccharide levels in the blood.

As the levels of these hormones diminish in perimenopause, the vaginal mucosa becomes susceptible to infection, indicating their major regulatory function in local and systemic immunity.

In the same way, they may cause the intestinal epithelium to become abnormally permeable, allowing microbes to translocate. This hypothesis requires further research.

References

• Peters BA, et al. (2022). Spotlight on the gut microbiome in menopause: current insights. International Journal of Women’s Health. https://doi.org/10.2147%2FIJWH.S340491. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9379122/.
• Park MG, et al. (2023). Menopausal changes in the microbiome—a review focused on the genitourinary microbiome. Diagnostics (Basel). https://doi.org/10.3390%2Fdiagnostics13061193. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047399/.
• Laniewski P, et al. (2023). Connecting microbiome and menopause for healthy ageing. Nature Microbiology. doi: https://doi.org/10.1038%2Fs41564-022-01071-6. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9977513/.

Further Reading

• All Menopause Content
• What is Menopause?
• Causes of Menopause
• The Dangers of Ignorance Surrounding Menopause
• What Should I Eat During Menopause?

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.